MODIFIED HIPPOCAMPAL LONG-TERM POTENTIATION IN PKC-GAMMA-MUTANT MICE

Calcium-phospholipid-dependent protein kinase (PKC) has long been sugg ested to play an important role in modulating synaptic efficacy. We ha ve created a strain of mice that lacks the gamma subtype of PKC to eva luate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synapti c transmission that is indistinguishable from wild-type mice. Long-ter m potentiation (LTP), however, is greatly diminished in mutant animals , while two other forms of synaptic plasticity, long-term depression a nd paired-pulse facilitation, are normal. Surprisingly, when tetanus t o evoke LTP was preceded by a low frequency stimulation, mutant animal s displayed apparently normal LTP. We propose that PKCgamma is not par t of the molecular machinery that produces LTP but is a key regulatory component.